Synthesis of Enhanced, Isolable Disulfanium Salts and their Application to Thiiranium-Promoted Polyene Cyclizations

Article abstract of DOI:10.1055/s-0037-1609754

Although electrophile-promoted polyene cyclizations have long been a mainstay transformation for the rapid and stereocontrolled preparation of varied natural products and designed molecules, efforts to effect sulfur-promoted variants have arguably lagged behind other counterparts. This state of affairs is particularly true with alkyl sulfide-based electrophiles, even in racemic variants. Herein, building on previously reported discoveries, is described a distinct and modular method to prepare a range of isolable alkyl and aryl disulfanium salts that can affect thiiranium-based polyene cyclizations in moderate to good yields. In most of the substrates probed, these reagents provide superior yields to previously reported alternatives. In addition, initial efforts to develop an asymmetric variant of the process through the use of chiral versions of these reagents are discussed.

Full text of DOI:10.1055/s-0037-1609754

SYNTHESIS
0
0
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1
1
4
3
7
-
2
1
0
X
©
Georg Thieme Verlag Stuttgart · New York
2018, 50, A–H
special topic
A
en
Synthesis
C. J. F. Cole et al.
Special Topic
Synthesis of Enhanced, Isolable Disulfanium Salts and their Appli-
cation to Thiiranium-Promoted Polyene Cyclizations
Charles J. F. Cole
Hyung Min Chi
0
0
0
0
0-
0
0
3
4-
3
1
3
7-
5
6
0
RS
S
SbCl6
Kenneth C. DeBacker
Scott A. Snyder*
0
0
0
0
0-
0
0
3
3-
5
9
4
8-
7
6
9
CH Cl , 0 °C
RS
2
2
H
5
min
1
4 examples
The University of Chicago, Department of Chemistry,
735 S. Ellis Avenue, Chicago, IL 60637, USA
sasnyder@uchicago.edu
•
•
Isolable and readily variable disulfanium salts where R = alkyl and aryl
Generally higher yielding than other electrophilic sulfur transfer reagents for
polyene cyclizations with yields up to 64%
5
Dedicated to Prof. Scott E. Denmark on the occasion of his 65th
birthday.
Published as part of the Special Section dedicated to Scott E. Den-
th
mark on the occasion of his 65 birthday.
Received: 15.03.2018
Accepted after revision: 09.04.2018
Published online: 14.06.2018
At the time of our initial investigations, the Denmark
group had already developed a powerful chiral Lewis base
DOI: 10.1055/s-0037-1609754; Art ID: ss-2018-c0184-st
promoted cyclization to afford monocyclic sulfides such as
4
2
(Scheme 1). High enantiocontrol was achieved through
Abstract Although electrophile-promoted polyene cyclizations have
long been a mainstay transformation for the rapid and stereocontrolled
preparation of varied natural products and designed molecules, efforts
to effect sulfur-promoted variants have arguably lagged behind other
counterparts. This state of affairs is particularly true with alkyl sulfide-
based electrophiles, even in racemic variants. Herein, building on previ-
ously reported discoveries, is described a distinct and modular method
to prepare a range of isolable alkyl and aryl disulfanium salts that can
affect thiiranium-based polyene cyclizations in moderate to good
yields. In most of the substrates probed, these reagents provide superi-
or yields to previously reported alternatives. In addition, initial efforts to
develop an asymmetric variant of the process through the use of chiral
versions of these reagents are discussed.
the generation of configurationally stable phenylthiiranium
ions in the presence of a chiral selenophosphoramide cata-
lyst. Extensions of that system to polyene cyclizations were
not yet reported (vide infra), with the only examples in the
literature for those processes being racemic events using
aryl sulfide based electrophiles with electron-rich termi-
nating groups, such as the conversion of 3 into 4 as achieved
5
by Livinghouse. We recently found that linear dialkyl sulfa-
nium salts of type 6, generated by combining SbCl with
5
1
,2-dithioethers and Cl , could cyclize an array of electron-
2
rich as well as electron-neutral and -deficient substrates in
acceptable to good yields, ultimately incorporating three
different alkyl sulfide groups onto the respective frame-
Key words alkyl sulfide, sulfuryl dichloride, disulfanium salts, geranyl
acetate, tetrahydrothiophene, SbCl5
6
works. We also discovered that these reagents often per-
formed better than other commercially available electro-
philic alkyl sulfide reagents such as dimethyl(meth-
ylthio)sulfonium tetrafluoroborate (DMTSF).7
Over the past decade, there has been a resurgence of in-
terest in developing improved and more powerful reagents
to affect both racemic and enantioselective electrophile-
Just a short while ago, the Denmark group, in a land-
mark discovery contemporaneous with these efforts, re-
ported the first cases of effective asymmetric polyene cy-
1
promoted polyene cyclizations. One area where we have
tried to contribute, in particular, has been in the develop-
ment of better tools to promote halonium-based polyene
cyclizations. A key finding was the discovery that the com-
bination of a Lewis acid (SbCl ), a Lewis base (Et S), and
8
clizations initiated by thiiranium ions. Their process used
an appropriate chiral Lewis base with a distinct aryl sulfide
electrophile in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) to
convert electron-rich substrates such as 5 into 8 in good
yield and with high levels of enantioselectivity. Despite this
important advance, effecting the same reactions, even in ra-
cemic form, remains particularly challenging for alkyl sul-
fide-based systems, with additional tools beyond those of
type 6 likely needed. Herein, we report a different approach
for the preparation of a variety of isolable and reactive al-
kylsulfanium species, one that enhances significantly the
5
2
molecular halogens (X ) could create a suite of reagents
2
with broad applicability to effect racemic cyclizations in-
corporating chlorine, bromine, and iodine atoms, even with
2
historically challenging substrates. More recent explora-
tions have questioned whether related designs, which re-
flect the Denmark paradigm of Lewis base activation of a
3
Lewis acid, could also generate potent sulfur-based elec-
trophilic species.
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–H

B
Synthesis
C. J. F. Cole et al.
Special Topic
chiral Lewis base
phthalimide-SPh
combined tetrahydrothiophene with SbCl and an array of
5
sulfenyl chlorides generated either from commercial disul-
fide or thiol precursors using known procedures.10 Follow-
ing stirring of those three components at 0 °C for 30 min-
utes, subsequent filtration provided an array of semi-crys-
talline thiolane-based disulfanium salts 12–18 in yields
greater than 90% on 1 mmol scale. Just like our previously
prepared salts of type 6 (cf. Scheme 1),6 these materials
were challenging to characterize based on their seeming in-
stability when dissolved in organic solvents. As such, their
structures are assumed based on stoichiometry and the
Pasquato precedent.9 Despite that solvolytic instability,
however, these materials were stable when stored at –20 °C
for several months with disulfanium salt 12 retaining com-
plete reactivity even when stored at 10 °C for one week.
O
O
1
O
EtSO3H
O
CH2Cl2
SPh
–20 °C, 3 d
2
(92%, 97:3 er)
OMe
OMe
OMe
OMe
PhSOMe
BF3
MeNO2
5
min
PhS
(
51%)
H
3
4
R
R
S
S
SbCl6
Cl
S
RS
S
6
R
S
RSH
or
MeNO2
min
16–74%)
H
SO2Cl2
SbCl6
5
RSCl
5
7: R = H, Me, CF2CH2
SbCl5
(
RS SR
Isolable solids
stable at –20 °C
for >2 months
30 min
0
°C
chiral Lewis base
phthalimide-SAryl
HFIP
i-Pr
S
i-Pr
F3C
S
S
S
22 °C, 12 h
H
S
S
SbCl6
SbCl6
S
SbCl6
(
60%, 90:10 er)
5
8
12 (96%)
13 (92%)
14 (95%)
SMe
HN
SMe
Et
Et
O
MeSCl
S
S
S
S
Et
Et
S
S
S
S
SbCl5
MeCN, H2O
78 °C, 2 h
80%, 93:7 er)
SbCl6
SbCl6
–
SbCl6
(
9
10
11
15 (91%)
16 (95%)
Scheme 1 Leading examples of C–C bond-forming cyclizations initiat-
ed by electrophilic sulfur reagents and inspiration for the design of new
electrophilic tools
N
S
S
S
S
S
SbCl6
SbCl6
overall array of alkyl sulfides that can be directly incorpo-
rated into polyene cyclization products. Importantly, in-
creased yields are observed for many substrates, particular-
ly variants that performed poorly with reagents of type 6.
We also show that chiral versions of these reagents can af-
ford modest levels of enantioselection.
1
7 (94%)
18 (92%)
Scheme 2 Preparation of cycloalkyl disulfanium salts
To evaluate the power of this diverse array of new tools,
each was reacted with substrate 5 to afford products 19–25
as shown in Table 1. In all cases, yields for the cyclization
were good, ranging from 43–64%. Of note, relative to the
yields we previously obtained for 19 and 20 using reagents
Our design for new alkyl- and aryl sulfide electrophiles
was inspired by the work of Pasquato and co-workers,
wherein a potent alkyl sulfide electrophile was generated
by the reaction of a chiral cyclic disulfide with MeSCl in the
6
of type 6 (cf. Scheme 1), higher throughputs were obtained
9
presence of SbCl5. This species could generate products
with salts 12 and 13, while 14 was effectively commensu-
rate in efficiency in producing 21 (Table 1, entries 1–3). Sig-
nificantly, however, more hindered alkyl sulfides that we
found challenging to prepare and utilize in reagent form 6,
such as those leading to the benzyl and isopropyl congeners
22 and 23, worked quite well here. For reasons that are
presently unclear to us, compound 22 was initially obtained
as a 4:1 mixture of diastereomers, though the major diaste-
such as 11 following asymmetric thiiranium opening with
acetonitrile. We wondered if the use of a cyclic monosulfide
could achieve appropriate activation of a variety of sulfides,
hoping that with the right cyclic sulfide perhaps a more
strained sulfonium species could be generated that could
lead to even more effective sulfur transfer. As shown in
Scheme 2, our optimized variant of that synthetic process
6
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–H

C
Synthesis
C. J. F. Cole et al.
Special Topic
reomer could be isolated in pure form; all other substrates
effectively afforded single products. Finally, the aryl-based
reagents performed equally well, with the success of re-
agent 18 providing a reactive handle within product 25 to
potentially affect a Julia–Kocienski coupling if desired.11
Worth noting is that strain within the reagents might be
partially responsible for the efficiency of these transforma-
tions, as use of the 6-membered counterpart of 13 afforded
chiral selection observed was generally low (55:45 er at
best) (Scheme 3). Of note, some differences in both yield
and enantioselection were observed based on the electro-
phile used (reagent 41 vs 42), though it is hard to say at this
point whether there is a great difference based on scaffold
geometry (reagent 41 vs 43).
chiral
sulfanium salt
41, 42, or 43
OH
OAc
20 in slightly inferior yield (58%, compared to 64% in entry
OAc
2); the more highly strained 4-membered sulfide was not
RS
CH2Cl2
–78 °C, 2 h
probed.
36
40
Table 1 Electrophilic Sulfur-Promoted Polyene Cyclization of Homo-
geranyl Benzene 5 Employing Disulfanium Salts 12–18
MeS
S
PhS
S
SbCl6
SbCl6
S
MeS
SbCl6
RS
4
1
42
43
38%, 6% ee
S
SbCl6
3
6%, 3% ee
53%, 10% ee
Scheme 3 Preliminary reaction of chiral disulfanium salts 41, 42, and
12–18
4
3 with geranyl acetate (36)
CH2Cl2, 0 °C
min
RS
H
5
5
19–25
In conclusion, a more modular and variable approach
Entry
Sulfur reagent
Product
Yield
Previous yield (%)
from ref. 6
has been developed to readily prepare an array of electro-
philic sulfur transfer reagents that possess stability appro-
priate to storage, and also seem to have enhanced reactivity
relative to previously explored thiiranium sources, particu-
larly those that are alkyl-based. Future work seeks to build
on these results, both in terms of generating additional
electrophilic reagents of broad types based on this design as
well as rendering these processes efficient with regards to
enantioselection.13
(
%)
1
2
3
4
5
6
12 (R = Me)
13 (R = Et)
19
20
21
22
23
24
25
55
64
54
43a
50
45
64
42
52
14 (R = CF
3
CH
2
CH
2
)
55
15 (R = Bn)
trace
trace
–
16 (R = i-Pr)
17 (R = Ph)
7
18 (R = heteroaryl)
–
a
Initially obtained as a 4:1 mixture of diastereomers; major diastereomer
isolated in 35% yield.
All reactions were carried out under an argon atmosphere with anhy-
drous solvents under anhydrous conditions, unless otherwise noted.
Anhydrous THF, toluene, Et O, CH Cl , and MeCN were obtained by
To assess substrate scope in a broader sense, we elected
to use reagent 13 for those purposes, viewing an ethyl-
based electrophile as being arguably less reactive than
some of the other alkyl-based alternatives (such as 12 and
2
2
2
passing commercially available pre-dried, oxygen-free formulations
through activated alumina columns. Yields refer to chromatographi-
1
13
cally and spectroscopically ( H and C NMR) homogeneous materials,
unless otherwise stated. Reagents were purchased at the highest
commercial quality and used without further purification, unless
otherwise stated. Reactions were magnetically stirred and monitored
by TLC carried out on 0.25 mm Merck silica gel plates (60F-254) using
UV light as visualizing agent, and an aqueous solution of cerium am-
1
4) on both steric and electronic grounds. It was also an ef-
fective counterpoint to evaluate the reagent previously gen-
6
erated of type 6 that could also transfer an ethyl sulfide
unit. Table 2 provides the seven substrates that we have
probed to date, including both electron-rich (Table 2, en-
tries 1–5) as well as electron-deficient (entries 6 and 7) ma-
terials. With the exception of substrate 30, reagent 13 out-
performed the reagents of type 6 we previously prepared,6
in some cases providing product where none had been ob-
served before (entries 1 and 2), and in another more than
doubling the throughput (entry 7).
Finally, to assess whether chiral, cyclic monosulfides
could afford appropriate reagents for chiral transfer, we
prepared three variants possessing two different scaffolds
and two different electrophilic sulfur species for transfer.12
In all cases, cyclization of 36 to 40 was achieved, though the
monium molybdate or a solution of KMnO4 in aqueous NaHCO and
3
2f
heat as developing agents. (2R,5R)-2,5-Dimethylthiolane, 2-benzo-
14
thiazole disulfide, and all monoalkene and polyene cyclization sub-
6
strates were prepared according to the procedures described in the
literature. SiliCycle silica gel (60, academic grade, particle size 0.040–
0.063 mm) was used for flash column chromatography. Preparative
TLC separations were carried out on 0.50 mm E. Merck silica gel
plates (60F-254). NMR spectra were recorded on Bruker 400 and 500
MHz instruments and calibrated using residual undeuterated solvent
as an internal reference. Standard abbreviations were used to explain
the multiplicities. IR spectra were recorded on a PerkinElmer 1000
series FT-IR spectrophotometer. High-resolution mass spectra
(HRMS) were recorded on Agilent 6244 Tof-MS using ESI (electro-
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–H

D
Synthesis
C. J. F. Cole et al.
Special Topic
Table 2 Scope of Diverse Monoalkenes and Polyenes Cyclizations as Effected with Ethyldisulfanium Salt 12
S
S
R1
R2
SbCl6
R1
13
R2
CH2Cl2, 0 °C
EtS
5
min
Entry
1
Substrate
Product
Yield (%)
55
Previous yield (%) from ref. 6
EtS
0
2
2
6
8
27
2
3
28
0
OMe
EtS
OMe
29
OMe
OMe
OMe
OMe
10a
52
EtS
3
0
31
OMe
OMe
4
50
50
EtS
H
3
2
33
OMe
OMe
OMe
OMe
5
6
37
29
EtS
H
3
3
4
6
35
OH
OAc
OAc
42
47
35
20
EtS
3
7
OH
O
O
O
7
EtS
H
3
8
3
9
a
Protocyclization observed: 10%.
spray ionization) at the University of Chicago Mass Spectroscopy Core
Facility. All er values were determined by HPLC on a Daicel CHIRAL-
CEL OD-H column.
equiv) dropwise. This mixture was stirred at 0 °C for 30 min, unless
otherwise specified, and subsequently transferred to a flask contain-
ing tetrahydrothiophene (0.089 mL, 1.0 mmol, 1.0 equiv) in CH Cl2
2
(1.0 mL) at 0 °C followed by the dropwise addition of SbCl5 (1.0 M
solution in CH Cl , 1.0 mL, 1.0 mmol, 1.0 equiv). Upon completion,
pentane (5 mL) was added and the mixture filtered to give the desired
disulfanium salt as a semi-crystalline solid. The salt was dried under
Disulfanium Salts; General Procedure
2
2
To a solution of the thiol or alkyl disulfide (1.0 mmol, 1.0 equiv) in
CH Cl (1 mL) at 0 °C was added SO Cl (0.090 mL, 1.1 mmol, 1.1
2
2
2
2
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Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–H

E
Synthesis
C. J. F. Cole et al.
Special Topic
vacuum for 10–20 min and then immediately stored at –20 °C. Due to
their instability in typical organic solvents at 23 °C, all salts were
characterized by ATR-FTIR spectroscopy and melting point analysis.
organic layers were combined, dried (Na SO ), and concentrated to
give a crude residue, which was further purified by flash column
chromatography or preparative TLC as indicated.
2
4
Methyl Disulfanium Salt (12)
Methyl(1,1,4a-trimethyl-1,2,3,4,4a,9,10,10a-octahydrophenan-
thren-2-yl)sulfane (19)
Prepared from Me2S2 following the procedure above at –20 °C to af-
ford 12 as a deep purple solid (0.450 g, 96%); mp 101–102 °C.
The crude material was purified by flash column chromatography
IR (film): 3337, 3005, 2942, 1444, 1306, 1271, 965, 872, 687 cm–1
(hexanes/CH
2
Cl , 4:1), followed by preparative TLC (hexanes/CH Cl ,
2
2
2
.
3:1) to afford 19 as a colorless oil (15.0 mg, 55%); R = 0.25 (hex-
f
anes/CH Cl , 4:1).
2
2
Ethyl Disulfanium Salt (13)
1
H NMR (500 MHz, CDCl ): δ = 7.24 (dd, J = 7.8, 1.4 Hz, 1 H), 7.13 (tdt,
3
Prepared from Et S following the procedure above to afford 13 as an
2
2
J = 7.7, 1.6, 0.8 Hz, 1 H), 7.08 (td, J = 7.3, 1.4 Hz, 1 H), 7.06–7.03 (m, 1
H), 3.00–2.83 (m, 2 H), 2.38 (dt, J = 13.1, 3.4 Hz, 1 H), 2.29 (dd, J = 12.7,
off-white solid (0.444 g, 92%); mp 88–89 °C.
IR (film): 3006, 2954, 2870, 1445, 1302, 1269, 1249, 893, 669 cm–1
.
4.0 Hz, 1 H), 2.15 (s, 3 H), 2.12–2.06 (m, 1 H), 1.97–1.89 (m, 2 H),
1
.82–1.70 (m, 1 H), 1.54–1.46 (m, 1 H), 1.39 (dd, J = 12.2, 2.2 Hz, 1 H),
3,3,3-Trifluoropropyl Disulfanium Salt (14)
1.22 (s, 3 H), 1.21 (s, 3 H), 0.94 (s, 3 H).
Prepared from 3,3,3-trifluoropropane thiol following the procedure
above to afford 14 as a grey solid (0.523 g, 95%); mp 75–78 °C.
Note that all NMR data matched that previously reported.6
IR (film): 2996, 2947, 1309, 1240, 1139, 1094, 870, 634 cm–1
.
Ethyl(1,1,4a-trimethyl-1,2,3,4,4a,9,10,10a-octahydrophenan-
thren-2-yl)sulfane (20)
Benzyl Disulfanium Salt (15)
The crude material was purified by flash column chromatography
Prepared from benzyl mercaptan following the procedure above to af-
(hexanes/CH
2
Cl
2
, 4:1), followed by preparative TLC (hexanes/CH
2 2
Cl ,
ford 15 as an orange-yellow solid (0.496 g, 91%); mp 64–65 °C.
3:1) to afford 20 as a colorless oil (18.0 mg, 64%); R
f
= 0.25 (hex-
IR (film): 2943, 1453, 1410, 1306, 1246, 872, 696 cm–1
.
anes/CH Cl , 4:1).
2 2
1
H NMR (500 MHz, CDCl ): δ = 7.24 (dd, J = 7.9, 1.4 Hz, 1 H), 7.16–7.11
3
(
m, 1 H), 7.08 (td, J = 7.3, 1.4 Hz, 1 H), 7.06–7.03 (m, 1 H), 2.96 (ddd, J =
Isopropyl Disulfanium Salt (16)
1
7.2, 6.6, 1.9 Hz, 1 H), 2.87 (ddd, J = 17.4, 11.6, 7.2 Hz, 1 H), 2.58 (qq,
J = 12.4, 7.4 Hz, 2 H), 2.39–2.33 (m, 2 H), 2.06 (dq, J = 14.0, 3.8 Hz, 1 H),
.02–1.90 (m, 2 H), 1.82–1.70 (m, 1 H), 1.61–1.47 (m, 2 H), 1.39 (dd,
Prepared from isopropyl mercaptan following the procedure above to
afford 16 as an off-white solid (0.472 g, 95%); mp 107–109 °C.
IR (film): 2949, 1443, 1411, 1306, 1249, 1048, 874 cm–1
2
.
J = 12.2, 2.2 Hz, 1 H), 1.27 (t, J = 7.4 Hz, 3 H), 1.22 (s, 6 H), 0.93 (s, 3 H).
Note that all NMR data matched that previously reported.6
Phenyl Disulfanium Salt (17)
Prepared from Ph2S following the procedure above, starting at 0 °C
and slowly warming to 23 °C to afford 17 as a pale orange solid (0.500
g, 91%); mp 108–110 °C.
2
(3,3,3-Trifluoropropyl)(1,1,4a-trimethyl-1,2,3,4,4a,9,10,10a-octa-
hydrophenanthren-2-yl)sulfane (21)
The crude material was purified by flash column chromatography
IR (film): 2994, 2945, 1442, 1400, 1305, 1270, 1247, 862, 764, 703,
(
hexanes/CH Cl , 4:1), followed by preparative TLC (hexanes/CH Cl ,
2
2
2
2
–1
690 cm
.
3
:1) to afford 21 as a colorless oil (19.0 mg, 54%); R = 0.35 (hex-
f
anes/CH Cl , 4:1).
2
2
2-Benzothiazole Disulfanium Salt (18)
1
H NMR (500 MHz, CDCl ): δ = 7.23 (dd, J = 8.0, 1.4 Hz, 1 H), 7.13 (td,
3
Prepared from benzothiazole disulfide following the procedure above
starting at 0 °C and heating to reflux to afford 18 as a bright yellow
solid (0.541 g, 92%); mp 118–119 °C.
J = 7.5, 1.7 Hz, 1 H), 7.09 (td, J = 7.3, 1.4 Hz, 1 H), 7.05 (dd, J = 7.5, 1.6
Hz, 1 H), 2.96 (ddd, J = 17.3, 6.7, 1.9 Hz, 1 H), 2.91–2.84 (m, 1 H), 2.72
(qdd, J = 12.8, 9.7, 6.5 Hz, 2 H), 2.43–2.37 (m, 2 H), 2.36–2.33 (m, 2 H),
2.07–1.90 (m, 3 H), 1.82–1.70 (m, 1 H), 1.51 (ddd, J = 13.0, 10.9, 4.4
Hz, 1 H), 1.40 (dd, J = 12.1, 2.2 Hz, 1 H), 1.22 (s, 3 H), 1.21 (s, 3 H), 0.93
IR (film): 3064, 1427, 1312, 1237, 1005, 756, 705, 669 cm–1
.
(s, 3 H).
Chiral Phenyl Disulfanium Salt (42)
Note that all NMR data matched that previously reported.6
Prepared from Ph2S2 and (2R,5R)-2,5-dimethylthiolane following the
procedure above, starting at 0 °C and slowly warming to 23 °C to af-
ford 42 as a black solid (0.453 g, 94%); mp 92–93 °C.
Benzyl(1,1,4a-trimethyl-1,2,3,4,4a,9,10,10a-octahydrophenan-
thren-2-yl)sulfane (22)
IR (film): 2976, 2912, 1442, 1307, 1251, 999, 751, 684 cm–1
.
The crude material was obtained as a mixture of diastereomers (4:1),
which was purified by flash column chromatography (hexanes/CH Cl ,
2
2
Thiiranium-Promoted Polyene Cyclizations Using Reagents 12–18;
General Procedure
2
0:1), followed by preparative TLC (hexanes/CH Cl , 3:1) to afford the
2 2
major diastereomer 22 as a pale yellow oil (11.4 mg, 35%); R = 0.30
f
To a solution of the alkene substrate (0.1 mmol, 1.0 equiv) in CH Cl
2
2
(
hexanes/CH Cl , 4:1).
2 2
(2.5 mL) at 0 °C was quickly added a solution of the disulfanium salt
IR (film): 3060, 3026, 2965, 2927, 1489, 1453, 1389, 756, 701 cm–1
.
(
0.11 mmol, 1.1 equiv) in CH Cl (0.25 mL) in a single portion (see Ta-
2
2
1
bles 1 and 2). After stirring the resultant mixture for 5 min, the reac-
H NMR (500 MHz, CDCl ): δ = 7.33–7.27 (m, 4 H), 7.21 (dd, J = 7.7, 1.7
3
tion contents were quenched by the addition of a sat. aq. NaHCO (5
Hz, 2 H), 7.11 (t, J = 6.2 Hz, 1 H), 7.06 (dt, J = 7.1, 1.4 Hz, 1 H), 7.02 (dd,
J = 7.2, 1.6 Hz, 1 H), 3.78 (d, J = 13.3 Hz, 1 H), 3.72 (d, J = 13.3 Hz, 1 H),
3
mL) and the aqueous layer was extracted with CH Cl (3 × 5 mL). The
2
2
2.96 (dd, J = 16.8, 6.8 Hz, 1 H), 2.82 (ddd, J = 17.5, 11.6, 7.3 Hz, 1 H),
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–H

F
Synthesis
C. J. F. Cole et al.
Special Topic
2
1
.31 (dt, J = 13.1, 3.4 Hz, 1 H), 2.27–2.20 (m, 1 H), 2.00–1.91 (m, 2 H),
.87 (ddt, J = 13.4, 7.3, 2.1 Hz, 1 H), 1.72 (dtd, J = 13.4, 11.9, 6.7 Hz, 1
7.06 (dd, J = 7.5, 1.7 Hz, 1 H), 3.95 (dd, J = 12.8, 4.1 Hz, 1 H), 3.03–2.86
(m, 2 H), 2.40 (dt, J = 13.1, 3.5 Hz, 1 H), 2.32 (dq, J = 13.9, 3.8 Hz, 1 H),
2.15 (qd, J = 13.5, 3.4 Hz, 1 H), 1.97 (ddt, J = 13.3, 7.1, 2.1 Hz, 1 H),
1.87–1.69 (m, 3 H), 1.61 (dd, J = 12.2, 2.2 Hz, 1 H), 1.28 (s, 3 H), 1.27 (s,
3 H), 1.06 (s, 3 H).
H), 1.45–1.35 (m, 1 H), 1.30–1.25 (m, 2 H), 1.20 (s, 3 H), 1.05 (s, 3 H),
0.91 (s, 3 H).
13
C NMR (126 MHz, CDCl ): δ = 149.5, 139.0, 135.1, 129.1, 129.1, 56.4,
3
13
52.1, 39.2, 38.5, 37.9, 36.6, 30.8, 29.6, 28.0, 24.9, 19.9, 17.8.
C NMR (126 MHz, CDCl ): δ = 167.6, 153.5, 149.2, 135.5, 135.0,
3
HRMS (ESI): m/z [M + H]+ calcd for C24H31S+: 351.2141; found:
51.2142.
129.1, 126.1, 126.0, 125.7, 124.6, 124.2, 121.7, 121.0, 60.6, 52.2, 39.2,
8.8, 37.9, 30.8, 30.0, 28.4, 25.0, 20.0, 18.2.
HRMS (ESI): m/z [M + H]+ calcd for C24H28NS2+: 394.1658; found:
94.1650.
3
3
3
Isopropyl(1,1,4a-trimethyl-1,2,3,4,4a,9,10,10a-octahydrophenan-
thren-2-yl)sulfane (23)
(
(
1,1-Dimethyl-1,2,3,4-tetrahydronaphthalen-2-yl)(ethyl)sulfane
27)
The crude material was purified by flash column chromatography
(
hexanes/CH Cl , 5:1), followed by preparative TLC (hexanes/CH Cl ,
2
2
2
2
3
:1) to afford 23 as a colorless oil (15.0 mg, 50%); R = 0.26 (hex-
The crude material was purified by preparative TLC (hexanes/CH Cl ,
2 2
f
anes/CH Cl , 4:1).
4:1) to afford 27 as a colorless oil (12.0 mg, 55%); R = 0.31 (hex-
2
2
f
IR (film): 3060, 2966, 2928, 2361, 1489, 1450, 1042, 758, 722 cm–1
.
anes/CH Cl , 4:1).
2 2
1
IR (film): 3026, 2964, 2927, 2868, 1489, 1457, 1263, 1042, 758, 700
H NMR (500 MHz, CDCl ): δ = 7.24 (dd, J = 7.9, 1.4 Hz, 1 H), 7.12 (t, J =
.7 Hz, 1 H), 7.08 (td, J = 7.3, 1.4 Hz, 1 H), 7.04 (dd, J = 7.6, 1.7 Hz, 1 H),
.00–2.83 (m, 3 H), 2.39–2.32 (m, 2 H), 2.07–1.90 (m, 3 H), 1.81–1.72
3
–1
cm
.
7
3
1
H NMR (500 MHz, CDCl ): δ = 7.30 (t, J = 7.6 Hz, 2 H), 7.24–7.17 (m, 2
3
(
1
0
1
m, 1 H), 1.51 (dt, J = 11.1, 6.6 Hz, 1 H), 1.40 (dd, J = 12.2, 2.2 Hz, 1 H),
.29 (d, J = 6.9 Hz, 3 H), 1.27 (d, J = 7.1 Hz, 3 H), 1.21 (d, J = 3.3 Hz, 6 H),
.92 (s, 3 H).
H), 3.13 (ddd, J = 14.2, 10.1, 4.6 Hz, 1 H), 2.84 (s, 1 H), 2.73–2.58 (m, 2
H), 2.46 (dd, J = 11.7, 2.3 Hz, 1 H), 2.08–1.99 (m, 1 H), 1.66–1.59 (m, 1
H), 1.29 (t, J = 7.5 Hz, 3 H), 1.27 (s, 3 H), 1.15 (s, 3 H).
13
3
C NMR (126 MHz, CDCl ): δ = 149.6, 135.2, 129.1, 125.9, 125.5,
C NMR (126 MHz, CDCl ): δ = 142.0, 128.60, 128.59, 128.57, 128.56,
3
3
1
2
24.6, 56.1, 52.3, 39.5, 38.5, 37.9, 35.3, 30.9, 29.8, 29.4, 25.0, 24.13,
4.07, 20.0, 17.7.
126.1, 72.8, 61.2, 34.7, 34.5, 29.0, 27.1, 25.7, 15.5.
HRMS (ESI): m/z [M + H]+ calcd for C14H21S+: 221.1358; found:
221.1356.
HRMS (ESI): m/z [M + H]+ calcd for C20H31S+: 303.2141; found:
03.2147.
3
(7-Methoxy-1,1-dimethyl-1,2,3,4-tetrahydronaphthalen-2-
Phenyl(1,1,4a-trimethyl-1,2,3,4,4a,9,10,10a-octahydrophenan-
thren-2-yl)sulfane (24)
yl)(ethyl)sulfane (29)
The crude material was purified by flash column chromatography
(hexanes/CH Cl , 2:1), followed by preparative TLC (hexanes/EtOAc,
The crude material was purified by flash column chromatography
2
2
(
hexanes/CH Cl , 4:1) to afford 24 as a colorless oil (15.1 mg, 45%); R =
20:1) to afford 29 as a pale yellow oil (6.8 mg, 28%); R = 0.74 (hex-
2
2
f
f
0
.33 (hexanes/CH Cl , 4:1).
anes/EtOAc, 4:1).
2
2
IR (film): 3070, 3057, 2965, 2935, 2360, 1456, 1437, 757, 734, 722,
IR (film): 2965, 2931, 2870, 2833, 1610, 1504, 1251, 1186, 1076,
–1
–1
691 cm
.
1046, 804 cm
.
1
1
H NMR (500 MHz, CDCl ): δ = 7.44–7.39 (m, 2 H), 7.32–7.25 (m, 2 H),
H NMR (500 MHz, CDCl ): δ = 6.96 (d, J = 8.4 Hz, 1 H), 6.87 (s, 1 H),
3
3
7
.23–7.18 (m, 2 H), 7.11 (td, J = 8.0, 7.5, 1.9 Hz, 1 H), 7.08 (td, J = 7.2,
.5 Hz, 1 H), 7.04 (dd, J = 7.6, 1.8 Hz, 1 H), 3.00–2.84 (m, 6.0 Hz, 3 H),
.31 (dt, J = 13.1, 3.4 Hz, 1 H), 2.08–1.99 (m, 2 H), 1.99–1.92 (m, 1 H),
.85–1.74 (m, 1 H), 1.51–1.47 (m, 1 H), 1.45 (dd, J = 12.2, 2.2 Hz, 1 H),
.32 (s, 3 H), 1.23 (s, 3 H), 1.04 (s, 3 H).
6.68 (d, J = 8.3 Hz, 1 H), 3.79 (s, 3 H), 2.88 (d, J = 16.8 Hz, 1 H), 2.82–
2.72 (m, 2 H), 2.67–2.56 (m, 2 H), 2.24–2.16 (m, 1 H), 2.06–1.95 (m, 1
H), 1.51 (s, 3 H), 1.33–1.25 (m, 6 H).
1
2
1
1
13
C NMR (126 MHz, CDCl ): δ = 158.0, 146.8, 129.8, 127.2, 112.5,
3
111.6, 55.4, 54.4, 39.1, 30.0, 29.2, 27.5, 27.3, 26.3, 15.1.
13
C NMR (126 MHz, CDCl ): δ = 149.4, 137.0, 135.1, 131.5, 129.1,
HRMS (ESI): m/z [M + H]+ calcd for C15H23OS : 251.1464; found:
+
3
1
3
29.0, 126.5, 125.9, 125.5, 124.6, 61.1, 52.4, 39.2, 38.8, 38.0, 30.9,
0.2, 28.1, 25.0, 19.9, 17.9.
251.1471.
HRMS (ESI): m/z [M + H]+ calcd for C23H29S+: 337.1984; found:
37.1983.
(6,7-Dimethoxy-1,1-dimethyl-1,2,3,4-tetrahydronaphthalen-2-
yl)(ethyl)sulfane (31)
3
The crude material was purified by flash column chromatography
(
2-Benzothiazole)(1,1,4a-trimethyl-1,2,3,4,4a,9,10,10a-octahy-
(
hexanes/EtOAc, 2:1) to afford 31 as a colorless oil (3.0 mg, 10%); R =
f
drophenanthren-2-yl)sulfane (25)
0
.47 (hexanes/EtOAc, 4:1).
The crude material was purified by flash column chromatography
1
H NMR (500 MHz, CDCl ): δ = 6.81 (s, 1 H), 6.51 (s, 1 H), 3.86 (s, 3 H),
3
(
hexanes/CH Cl , 1:1), followed by preparative TLC (hexanes/EtOAc,
2
2
3.83 (s, 3 H), 2.88–2.73 (m, 3 H), 2.68–2.56 (m, 2 H), 2.23–2.17 (m, 1
H), 2.05–1.97 (m, 1 H), 1.50 (s, 3 H), 1.30 (t, J = 7.3 Hz, 3 H), 1.28 (s, 3
H).
Note that all NMR data matched that previously reported.6
1
0:1) to afford 25 as a colorless oil (25.0 mg, 64%); R = 0.76 (hex-
f
anes/EtOAc, 4:1).
IR (film): 3060, 2964, 2942, 2360, 1456, 1426, 989, 755, 724 cm–1
.
1
H NMR (500 MHz, CDCl ): δ = 7.83 (d, J = 8.1 Hz, 1 H), 7.74 (dd, J = 8.0,
3
1.2 Hz, 1 H), 7.14 (td, J = 7.4, 1.7 Hz, 1 H), 7.10 (td, J = 7.3, 1.4 Hz, 1 H),
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–H

G
Synthesis
C. J. F. Cole et al.
Special Topic
Ethyl(6-methoxy-1,1,4a-trimethyl-1,2,3,4,4a,9,10,10a-octahy-
drophenanthren-2-yl)sulfane (33)
ter stirring for 2 h at –78 °C, the reaction mixture was quenched with
sat. aq. NaHCO (5 mL), warmed to 23 °C, and the aqueous layer was
3
extracted with CH Cl (3 × 5 mL). The organic layers were combined,
The crude material was purified by preparative TLC (hexanes/EtOAc,
2
2
dried (Na SO ), and concentrated to give a crude residue, which was
6
:1) to afford 33 as a colorless oil (16.0 mg, 50%); R = 0.73 (hex-
2
4
f
further purified by flash column chromatography (hexanes/EtOAc,
:1) to afford 40 as a colorless oil (17.0 mg, 53%, 45:55 er); R = 0.49
anes/EtOAc, 4:1).
3
1
f
H NMR (500 MHz, CDCl ): δ = 6.97 (dd, J = 8.4, 1.1 Hz, 1 H), 6.78 (d, J =
3
(hexanes/EtOAc, 1:1).
2
1
.7 Hz, 1 H), 6.67 (dd, J = 8.4, 2.6 Hz, 1 H), 3.77 (s, 3 H), 2.90 (ddd, J =
6.7, 6.5, 1.8 Hz, 1 H), 2.84–2.75 (m, 1 H), 2.58 (qq, J = 12.4, 7.4 Hz, 2
Note that similar reaction scales were used in the investigations with
the other chiral disulfanium salts.
H), 2.39–2.28 (m, 2 H), 2.05 (dq, J = 14.0, 3.8 Hz, 1 H), 2.00–1.88 (m, 2
H), 1.80–1.68 (m, 1 H), 1.50 (td, J = 13.2, 3.8 Hz, 1 H), 1.37 (dd, J = 12.1,
HPLC: OD-H column, 1.0 mL/min, hexanes/i-PrOH (9:1), 36 °C, 254
nm; t (major) = 6.37 min, t (minor) = 9.48 min (55:45 er).
2.2 Hz, 1 H), 1.26 (t, J = 7.4 Hz, 3 H), 1.23–1.19 (m, 6 H), 0.92 (s, 3 H).
R
R
Note that all NMR data matched that previously reported.6
IR (film): 3461, 3057, 2970, 2938, 2873, 1736, 1479, 1368, 1245,
–1
1026, 740, 692 cm .
(
6,7-Dimethoxy-1,1,4a-trimethyl-1,2,3,4,4a,9,10,10a-octahy-
1
H NMR (500 MHz, CDCl ): δ = 7.44–7.38 (m, 2 H), 7.29 (t, J = 8.4 Hz, 2
3
drophenanthren-2-yl)(ethyl) sulfane (35)
H), 7.25–7.20 (m, 1 H), 4.42 (dd, J = 11.8, 5.2 Hz, 1 H), 4.33 (dd, J =
11.8, 5.0 Hz, 1 H), 2.88 (dd, J = 12.5, 3.8 Hz, 1 H), 2.07 (s, 3 H), 1.95 (dq,
J = 14.2, 3.7 Hz, 1 H), 1.80 (dt, J = 13.1, 3.4 Hz, 1 H), 1.75–1.65 (m, 2 H),
1.46 (td, J = 13.5, 4.0 Hz, 1 H), 1.33 (s, 3 H), 1.23 (s, 3 H), 0.96 (s, 3 H).
13
The crude material was purified by flash column chromatography
(hexanes/EtOAc, 7:1), followed by preparative TLC (hexanes/EtOAc,
4
:1) to afford 35 as a colorless oil (12.8 mg, 37%); R = 0.48 (hex-
f
anes/EtOAc, 4:1).
1
C NMR (126 MHz, CDCl ): δ = 171.2, 136.4, 132.0, 129.1, 126.9, 72.1,
3
H NMR (500 MHz, CDCl ): δ = 6.73 (d, J = 2.8 Hz, 1 H), 6.52 (s, 1 H),
63.2, 60.7, 56.9, 42.6, 39.2, 29.9, 29.0, 23.8, 21.4, 17.6.
3
3
.84 (s, 3 H), 2.82 (qd, J = 16.8, 6.8 Hz, 2 H), 2.66–2.50 (m, 2 H), 2.33
HRMS (ESI): m/z [M + H+ – H O] calcd for C18H25O S+: 305.1570;
found: 305.1574.
2
2
(ddd, J = 28.6, 10.1, 3.5 Hz, 2 H), 2.09–2.01 (m, 1 H), 1.93 (dt, J = 17.5,
9
1
.6 Hz, 2 H), 1.73 (dt, J = 18.6, 11.9 Hz, 1 H), 1.49 (t, J = 13.2 Hz, 1 H),
.36 (d, J = 12.1 Hz, 1 H), 1.26 (t, J = 7.4 Hz, 3 H), 1.21 (d, J = 2.8 Hz, 6
H), 0.91 (s, 3 H).
Note that all NMR data matched that previously reported.6
Acknowledgment
We thank Dr. Florian Schevenels for the preparation of substrates 30,
2, and 34, Dr. Jennifer Pitzen for the preparation of substrate 38, Mr.
3
{
6-Hydroxy-2,2,6-trimethyl-3-[(ethyl)thio]cyclohexyl}methyl Ac-
Jonathan Keim and Mr. Minxing Shen for helpful discussions, and Dr.
Antoni Jurkiewicz and Dr. C. Jin Qin for assistance with NMR and mass
spectrometry, respectively. Financial support for this work came from
the University of Chicago and includes a Metcalf Fellowship that sup-
ported the work and training of K.C.D. during the summer of 2017.
etate (37)
The crude material was purified by flash column chromatography
(hexanes/EtOAc, 10:1 → 1:1) to afford 37 as a colorless oil (11.5 mg,
4
2%); R = 0.5 (hexanes/EtOAc, 1:1).
f
1
H NMR (500 MHz, CDCl ): δ = 4.38 (dd, J = 11.8, 5.4 Hz, 1 H), 4.31 (dd,
3
J = 11.9, 4.9 Hz, 1 H), 2.62–2.48 (m, 3 H), 2.34 (dd, J = 12.5, 3.8 Hz, 1 H),
2
.06 (s, 3 H), 1.98 (dq, J = 13.9, 3.6 Hz, 1 H), 1.84 (dt, J = 12.9, 3.3 Hz, 1
H), 1.69–1.57 (m, 2 H), 1.50 (td, J = 13.4, 3.7 Hz, 1 H), 1.25 (t, J = 7.4 Hz,
H), 1.23 (s, 3 H), 1.21 (s, 3 H), 0.85 (s, 3 H).
Supporting Information
3
Supporting information for this article is available online at
Note that all NMR data matched that previously reported.6
https://doi.org/10.1055/s-0037-1609754.
S
u
p
p
ortioIgnfmr oaitn
S
u
p
p
o
nrtogI
i
f
rm oaitn
5
(
-(Ethylthio)-4,4,7a-trimethylhexahydrobenzofuran-2(3H)-one
39)
The crude material was purified by flash column chromatography
hexanes/EtOAc, 10:1 → 1:1) to afford 39 as a colorless oil (11.4 mg,
References
(
1) For a recent review on cation-π cyclization chemistry see:
(
Snyder, S. A.; Levinson, A. M. In Comprehensive Organic Synthe-
sis, 2nd ed., Vol. 3, Part 5; Knochel, P.; Molander, G. A., Eds.;
Elsevier: Amsterdam, 2014, 268–291; and references cited
therein.
47%); R = 0.38 (hexanes/EtOAc, 4:1).
f
1
H NMR (500 MHz, CDCl ): δ = 2.57 (ttd, J = 12.4, 7.4, 5.0 Hz, 2 H), 2.48
3
(dd, J = 16.4, 14.7 Hz, 1 H), 2.43–2.37 (m, 1 H), 2.34 (dd, J = 16.3, 6.6
(2) (a) Snyder, S. A.; Treitler, D. S.; Brucks, A. P. J. Am. Chem. Soc.
Hz, 1 H), 2.24–2.15 (m, 1 H), 2.07–1.98 (m, 2 H), 1.74 (ddt, J = 9.0, 7.3,
2010, 132, 14303. (b) Snyder, S. A.; Treitler, D. S. Angew. Chem.
2.0 Hz, 2 H), 1.35 (s, 3 H), 1.26 (t, J = 7.4 Hz, 3 H), 1.13 (s, 3 H), 0.89 (s,
Int. Ed. 2009, 48, 7899. (c) Snyder, S. A.; Treitler, D. S.; Brucks, A.
P.; Sattler, W. J. Am. Chem. Soc. 2011, 133, 15898. (d) Snyder, S.
A.; Brucks, A. P.; Treitler, D. S.; Moga, I. J. Am. Chem. Soc. 2012,
3
H).
Note that all NMR data matched that previously reported.6
1
34, 17714. (e) Brucks, A. P.; Treitler, D. S.; Liu, S.-A.; Snyder, S.
5
-(Phenylthio)-4,4,7a-trimethylhexahydrobenzofuran-2(3H)-one
A. Synthesis 2013, 45, 1886. (f) Shen, M.; Kretschmer, M.; Brill, Z.
G.; Snyder, S. A. Org. Lett. 2016, 18, 5018.
(40)
To a solution of geranyl acetate (36; 0.021 mL, 0.1 mmol, 1.0 equiv) in
CH Cl (2.5 mL) at –78 °C was quickly added a solution of the chiral
phenyl disulfanium salt 42 (0.062 g, 0.11 mmol, 1.1 equiv, prepared
by same method described above) in CH Cl (0.25 mL) all at once. Af-
(3) (a) Denmark, S. E.; Beutner, G. L. Angew. Chem. Int. Ed. 2008, 47,
1560. (b) Hartmann, E.; Denmark, S. E. Helv. Chim. Acta 2017,
100, e1700158; doi: 10.1002/hlca.201700158.
2
2
2
2
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–H

H
Synthesis
C. J. F. Cole et al.
Special Topic
(
4) (a) Denmark, S. E.; Kornfilt, D. J. P.; Vogler, T. J. Am. Chem. Soc.
(10) For general preparative methods of alkyl and aryl sulfenyl chlo-
rides, see: (a) Organ, H. M. Methanesulfenyl Chloride, In Encyclo-
pedia of Reagents for Organic Synthesis; Wiley: New York, 2001.
(b) Zelčans, G.; Hutton, T. K.; Rios, R.; Shibata, N. Benzenesulfenyl
Chloride, In Encyclopedia of Reagents for Organic Synthesis;
Wiley: New York, 2001.
2011, 133, 15308. (b) Denmark, S. E.; Jaunet, A. J. Am. Chem. Soc.
2013, 135, 6419. (c) Denmark, S. E.; Chi, H. M. J. Am. Chem. Soc.
2014, 136, 8915.
(
5) (a) Edstrom, E.; Livinghouse, T. J. Chem. Soc., Chem. Commun.
1986, 279. (b) Edstrom, E.; Livinghouse, T. J. Am. Chem. Soc.
1986, 108, 1334. (c) Edstrom, E.; Livinghouse, T. J. Org. Chem.
1987, 52, 949. (d) Harring, S. R.; Livinghouse, T. J. Org. Chem.
1997, 62, 6388. For a more recent example, see: (e) Moore, J. T.;
8
(11) The recent polyene cyclization paper by Denmark illustrates
just such an example, indicating that the neighboring dimethyl
substituents do not prevent effective reaction.
Soldi, C.; Fettinger, J. C.; Shaw, J. T. Chem. Sci. 2013, 4, 292.
6) Schevenels, F. T.; Shen, M.; Snyder, S. A. Org. Lett. 2017, 19, 2.
7) For a review, see: (a) Adams, E. J.; Oscarson, S. Dimethyl(meth-
ylthio)sulfonium Tetrafluoroborate (DMTSF), In e-Encyclopedia of Reagents
for Organic Synthesis 2005, doi: 10.1002/047084289X.rd349.pub2. For
the original reagent disclosure, see: (b) Meerwein, H.; Zenner,
K.-F.; Gipp, R. Justus Liebigs Ann. Chem. 1965, 688, 67. For an
early reagent of related design, see: (c) Helmkamp, G. K.; Cassey,
H. N.; Olsen, B. A.; Pettitt, D. J. J. Org. Chem. 1965, 30, 933. For
representative uses in synthesis, see: (d) Trost, B. M.; Shibata, T.
J. Am. Chem. Soc. 1982, 104, 3225. (e) Trost, B. M.; Shibata, T.;
Martin, S. J. J. Am. Chem. Soc. 1982, 104, 3228. (f) Caserio, M. C.;
Kim, J. K. J. Am. Chem. Soc. 1982, 104, 3231. (g) Trost, B. M.;
Martin, S. F. J. Am. Chem. Soc. 1984, 106, 4263. (h) O’Malley, G. J.;
Cava, M. P. Tetrahedron Lett. 1985, 26, 6159.
(12) For selected examples using chiral sulfonium species see:
(a) Breau, L.; Ogilvie, W. W.; Durst, T. Tetrahedron Lett. 1990, 31,
35. (b) Julienne, K.; Metzner, P.; Henryon, V.; Greiner, A. J. Org.
Chem. 1998, 63, 4532. (c) Julienne, K.; Metzner, P.; Henryon, V.
(
(
J. Chem. Soc., Perkin Trans.
1 1999, 731. (d) Zanardi, J.;
Leriverend, C.; Aubert, D.; Julienne, K.; Metzner, P. J. Org. Chem.
2001, 66, 5620. (e) Zanardi, J.; Lamazure, D.; Minière, S.; Reboul,
V.; Metzner, P. J. Org Chem. 2002, 67, 9083. (f) Davoust, M.;
Cantagrel, F.; Metzner, P.; Brière, J.-F. Org. Biomol. Chem. 2008,
6, 1981. (g) Illa, O.; Namutebi, M.; Saha, C.; Ostovar, M.; Chen, C.
C.; Haddow, M. F.; Nocquet-Thibault, S.; Lusi, M.; McGarrigle, E.
M.; Aggarwal, V. K. J. Am. Chem. Soc. 2013, 135, 11951.
(13) For example, switching sulfides for certain diphosphines in this
same design has led to effective generation of HCl, HBr, DCl, and
DBr on laboratory scale: (a) Schevenels, F. T.; Shen, M.; Snyder,
S. A. J. Am. Chem. Soc. 2017, 139, 6329. For a general and excel-
lent set of reviews on the presence of sulfur in pharmaceutical
molecules, see: (b) Ilardi, R. A.; Vitaku, E.; Njardarson, J. T.
J. Med. Chem. 2014, 57, 2832. (c) Smith, B. R.; Eastman, C. M.;
Njardarson, J. T. J. Med. Chem. 2014, 57, 9764.
(8) Tao, Z.; Robb, K.; Zhao, K.; Denmark, S. E. J. Am. Chem. Soc. 2018,
140, 3569.
(9) Lucchini, V.; Modena, G.; Pasquato, L. J. Chem. Soc., Chem.
Commun. 1994, 13, 1565.
(14) Párkányi, C.; Abdelhamid, A. O. Heterocycles 1985, 23, 2917.
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Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–H